Augmenting Response to Entecavir With Peginterferon a-2a for the Treatment of HBeAg-positive Chronic Hepatitis B

Conditions

Chronic Hepatitis B

Keywords

Hepatitis B Entecavir pegylated interferon a-2a

Brief summary

The purpose of this study is to investigate whether it is possible to augment the response of patients with HBeAg-positive chronic hepatitis B to entecavir by using a temporary peginterferon alpha-2a add-on strategy

Brakenhoff SM, de Knegt RJ, van Campenhout MJH, van der Eijk AA, Brouwer WP, van Bömmel F, Boonstra A, Hansen BE, Berg T, Janssen HLA, de Man RA, Sonneveld MJ.

2022-07-0217 citations

10.1016/j.jmii.2022.06.002

Levels of Antibodies to Hepatitis B Core Antigen Are Associated With Liver Inflammation and Response to Peginterferon in Patients With Chronic Hepatitis B

Sylvia M. Brakenhoff, Robert J. de Knegt, Jeffrey Oliveira, Annemiek A. van der Eijk, Anneke J. van Vuuren et al. (10 authors)

The Journal of Infectious Diseases2022-05-2319 citations

10.1093/infdis/jiac210

Low hepatitis B surface antigen and HBV DNA levels predict response to the addition of pegylated interferon to entecavir in hepatitis B e antigen positive chronic hepatitis B

Kin Seng Liem, Margo J. H. van Campenhout, Qing Xie, Willem Pieter Brouwer, Heng Chi et al. (10 authors)

Alimentary Pharmacology & Therapeutics2019-01-2831 citations

10.1111/apt.15098

Interventions

DRUGpegylated interferon a-2a

180 μg, once per week s.c. for 24 weeks

DRUGEntecavir

0.5 mg once daily per os, either 72 weeks or 96 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Chronic hepatitis B (HBsAg positive \> 6 months) * HBeAg positive, anti-HBe negative at screening * ALT \> 1.3 x ULN within 60 days prior to screening and during screening * Liver biopsy performed within 2 years prior to screening or during screening * Age \> 18 years * Written informed consent * Adequate contraception for males and females during treatment and follow up; negative pregnancy test (for women of childbearing potential)

Exclusion criteria

* Antiviral therapy against HBV within the previous 6 months * Treatment with any investigational drug within 30 days of screening * Previous treatment with lamivudine or telbivudine for more than six months * Severe hepatitis activity as documented by ALT\>10 x ULN * History of decompensated cirrhosis (defined as jaundice in the presence of cirrhosis, ascites, bleeding gastric or esophageal varices or encephalopathy) * Pre-existent neutropenia (neutrophils \< 1,500/mm3) or thrombocytopenia (platelets \< 90,000/mm3) * Co-infection with hepatitis C virus or human immunodeficiency virus (HIV) * Other acquired or inherited causes of liver disease (i.e. alcoholic liver disease, obesity induced liver disease, drug related liver disease, auto-immune hepatitis, hemochromatosis, Wilson's disease or alpha-1 antitrypsin deficiency) * Alpha fetoprotein \> 50 ng/ml * Hyper- or hypothyroidism (subjects requiring medication to maintain TSH levels in the normal range are eligible if all other inclusion/

Design outcomes

Primary

Measure	Time frame
The combined presence of HBV DNA level < 200 IU/mL and HBeAg loss	week 48

Secondary

Measure	Time frame
The emergence of HBV polymerase mutations associated with reduced susceptibility to entecavir	up to week 96
Sustained response defined as the combined presence of HBV DNA level < 200 IU/mL and HBeAg loss	week 96
ALT normalization	up to week 96
Undetectable HBV DNA <60 IU/mL	up to week 96
HBsAg and HBeAg loss from serum	up to week 96

Countries

China, Netherlands, Poland, Romania, Turkey (Türkiye)

Outcome results

None listed